Abstract The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane, integral to all metazoan cells. It performs a critical structural role in the maintenance of nuclear architecture and integration of cytoskeletal structure in addition to aiding in regulation of gene expression, chromatin positioning, cell proliferation, migration and senescence. Exciting, recent work in Drosophila models and from Alzheimer?s diseases (AD) brain tissue has implicated a down regulation, specifically of B type lamins, and nucleoskeletal dysfunction as a critical step mediating the neurodegeneration associated with tauopathies such as AD. Lamin B1 (LB1) is the major B type lamin expressed in the mammalian CNS and loss of this protein during development results in significant defects in neuronal migration and cortical organization. We propose to test the hypothesis that overexpression of LB1 in neurons can provide a neuroprotective effect and ameliorate the phenotype in a mouse model of tau mediated neurodegeneration. The experiments we have proposed will allow us to test the intriguing possibility that modulating the levels of the nuclear lamina protein, LB1 can impact pathology in a clinically relevant mouse model of tau mediated Alzheimer?s disease